Combating bacteria with N-cycloalkyl-N&#39;-substituted-N&#39;-acyl-ureas

ABSTRACT

N-Cycloalkyl-N&#39;-substituted-N&#39;-acyl-ureas of the formula ##STR1## in which R 1  is cycloalkyl, 
     R 2  is cycloalkyl or optionally substituted phenyl, and 
     R 3  is cycloalkyl or substituted phenyl, 
     which are active against plant bacteria.

The invention relates to certain new substituted ureas, to a process fortheir preparation and to their use as plant bactericides.

It is known that certain copper compounds, for example copperoxychloride, have fungicidal and bactericidal properties. However, theiraction is not always satisfactory, especially in the case of lowconcentrations of active compound and when small amounts are applied.

The present invention now provides, as new compounds, the substitutedureas of the general formula ##STR2## in which

R¹ represents cycloalkyl,

R² represents cycloalkyl or optionally substituted phenyl and

R³ represents cycloalkyl or substituted phenyl.

The compounds of the formula (I) are distinguished by a high activityagainst bacteria which are harmful to plants and are thus of interest asplant protection agents.

Surprisingly, the substituted ureas according to the invention exhibit aconsiderably more powerful bactericidal action than compounds of thesame type of action which are known from the state of the art, forexample copper oxychloride.

Preferred compounds of the formula (I) are those in which

R¹ represents cyclohexyl,

R² represents cyclohexyl or 2,6-dialkyl-phenyl with 1 to 4 carbon atomsper alkyl radical and

R³ represents cyclohexyl or represents phenyl carrying one or moresubstituents selected from C₁ -C₄ -alkyl, C₁ -C₄ -alkoxy, halogen, C₁-C₂ -halogenoalkyl and nitro.

The invention also provides a process for the preparation of asubstituted urea of the formula (I) in which a carbodiimide of thegeneral formula

    R.sup.1 --N═C═N--R.sup.2                           (II),

in which R¹ and R² have the meanings indicated above, is reacted with acarboxylic acid of the general formula

    R.sup.3 --CO--OH                                           (III),

in which R³ has the meaning indicated above, if appropriate in thepresence of a tertiary amine and if appropriate using a diluent.

If, for example, a dicyclohexyl-carbodiimide and 4-methoxy-benzoic acidare used as starting substances, the reaction of these compounds can beoutlined by the following equation: ##STR3##

Formula (II) provides a definition of the carbodiimides to be used asstarting substances. Preferably, in this formula, R¹ and R² representthose radicals which have been mentioned as preferred in the definitionof the radicals R¹ and R² in formula (I).

Examples of the compounds (II) which may be mentioned are:dicyclohexyl-carbodiimide, N-(2,6-dimethyl-phenyl)-,N-(2,6-diethyl-phenyl)-, N-(2-methyl-6-ethyl-phenyl)-,N-(2,6-di-n-propyl-phenyl)-, N-(2,6-di-iso-propyl-phenyl)-,N-(2,6-di-n-butyl-phenyl)- andN-(2,6-di-iso-butyl-phenyl)-N'-cyclohexyl-carbodiimide.

The carbodiimides of the formula (II) are known compounds (seeMethodicum Chimicum, Volume 6 (1974), pages 783-794, Georg-Thieme-VerlagStuttgart and Academic Press New York, San Francisco, London). Theirpreparation from ureas or thioureas by splitting off water or hydrogensulphide is also known. Toluenesulphonic acid chloride can be used asthe condensing agent and hydrogen sulphide can be split off with leadcarbonate. The carbodiimides can furthermore be obtained by reaction ofcyclohexyl isocyanate with amines or anilines, water being split off.

Formula (III) provides a definition of the carboxylic acids also to beused as starting substances. Preferably, in this formula, R³ has themeaning indicated as preferred in the definition of the radical R³ informula (I).

Examples of the carboxylic acids of the formula (III) which may bementioned are: cyclohexanecarboxylic acid and 4-methyl-, 3-methyl-,2-methyl-, 4-iso-propyl-, 4-tert.-butyl-, 4-methoxy-, 3-methoxy-,2-chloro-, 3-chloro-, 4-chloro-, 2,4-dichloro-, 2,5-dichloro-,3,4-dichloro-, 2,6-dichloro, 2-bromo-, 3-bromo-, 4-bromo-, 3-fluoro-,4-fluoro-, 2-chloro-5-bromo-, 3-trifluoro-methyl-, 2-nitro-, 3-nitro-,4-nitro-, 5-chloro-2-nitro-, 4-chloro-3-nitro-, 2-methyl-3-nitro-,3-methyl-2-nitro-, 3-methyl-4-nitro-, 4-methyl-3-nitro- and5-methyl-2-nitrobenzoic acid.

The carboxylic acids of the formula (III) are generally known compoundscustomary in the laboratory.

The process for the preparation of the substitued ureas of the formula(I) is preferably carried out using a suitable solvent or diluent.Possible solvents and diluents are virtually any of the inert organicsolvents. These include, as preferences, aliphatic and aromatic,optionally chlorinated hydrocarbons, such as benzine, benzene, toluene,xylene, methylene chloride, chloroform, carbon tetrachloride,chlorobenzene and o-dichlorobenzene; ethers, such as diethyl ether,dibutyl ether, tetrahydrofuran and dioxane; ketones, such as acetone,methyl ethyl ketone, methyl isopropyl ketone and methyl isobutyl ketone;nitriles, such as acetonitrile and propionitrile; and alcohols, such asmethanol, ethanol and n- and isopropanol.

Examples of tertiary amines which can be employed as catalysts in theprocess according to the invention are trimethylamine, triethylamine,ethyl-di-isopropylamine, ethyl-di-cyclohexylamine, N,N-dimethylaniline,N,N-dimethyl-benzylamine and diaza-bicyclononane.

The reaction temperature can be varied within a substantial range. Ingeneral, the reaction is carried out at temperatures from 0° to 150° C.,preferably at 20° to 100° C.

The process according to the invention is in general carried out undernormal pressure.

The starting substances are usually employed in equimolar amounts forcarrying out the process according to the invention. An excess of one orthe other of the reactants brings no significant advantages. Thereaction is in general carried out in a suitable diluent in the presenceof a tertiary amine, and the reaction mixture is stirred at the requiredtemperature for several hours. After distilling off the solvent invacuo, the products are in general obtained in crystalline form. Themelting point is used for characterization of the products, which areusually purified by recrystallization.

The active compounds according to the invention exhibit a powerfulmicrobicidal action and can be employed in practice for combatingundesired micro-organisms. The active compounds are suitable for use asplant protection agents and can be employed as bactericides.

Bactericidal agents are employed in plant protection for combatingPseudomonadaceae, Rhizobiaceae, Enterobacteriaceae, Corynebacteriaceaeand Streptomycetaceae.

Thus, the active compounds according to the invention exhibit an actionagainst Xanthomonas oryzae in rice. In addition to an action afterapplication to the leaves, the present compounds also have a significantsystemic action, which can be detected after application to irrigationwater or to the soil.

The good toleration, by plants, of the active compounds, at theconcentrations required for combating plant diseases, permits treatmentof above-ground parts of plants, of vegetative propagation stock andseeds, of the soil and of irrigation water.

The active compounds can be converted into the customary formulations,such as solutions, emulsions, suspensions, powders, dusting agents,foams, pastes, soluble powders, granules, aerosols, suspension-emulsionconcentrates, seed-treatment powders, natural and synthetic materialsimpregnated with active compound, very fine capsules in polymericsubstances, coating compositions for use on seed, and formulations usedwith burning equipment, such as fumigating cartridges, fumigating cansand fumigating coils, as well as ULV cold mist and warm mistformulations.

These formulations may be produced in known manner, for example bymixing the active compounds with extenders, that is to say liquid orliquefied gaseous or solid diluents or carriers, optionally with the useof surface-active agents, that is to say emulsifying agents and/ordispersing agents and/or foam-forming agents. In the case of the use ofwater as an extender, organic solvents can, for example, also be used asauxiliary solvents.

As liquid diluents or carriers, especially solvents, there are suitablein the main, aromatic hydrocarbons, such as xylene, toluene or alkylnaphthalenes, chlorinated aromatic or chlorinated aliphatichydrocarbons, such as chlorobenzenes, chloroethylenes or methylenechloride, aliphatic or alicyclic hydrocarbons, such as cyclohexane orparaffins, for example mineral oil fractions, alcohols, such as butanolor glycol as well as their ethers and esters, ketones, such as acetone,methyl ethyl ketone, methyl isobutyl ketone or cyclohexanone, orstrongly polar solvents, such as dimethylformamide anddimethylsulphoxide, as well as water.

By liquefied gaseous diluents or carriers are meant liquids which wouldbe gaseous at normal temperature and under normal pressure, for exampleaerosol propellants, such as halogenated hydrocarbons as well as butane,propane, nitrogen and carbon dioxide.

As solid carriers there may be used ground natural minerals, such askaolins, clays, talc, chalk, quartz, attapulgite, montmorillonite ordiatomaceous earth, and ground synthetic minerals, such ashighly-dispersed silicic acid, alumina and silicates. As solid carriersfor granules there may be used crushed and fractionated natural rockssuch as calcite, marble, pumice, sepiolite and dolomite, as well assynthetic granules of inorganic and organic meals, and granules oforganic material such as sawdust, coconut shells, corn cobs and tobaccostalks.

As emulsifying and/or foam-forming agents there may be used non-ionicand anionic emulsifiers, such as polyoxyethylene-fatty acid esters,polyoxyethylene-fatty alcohol ethers, for example alkylaryl polyglycolethers, alkyl sulphonates, alkyl sulphates, aryl sulphonates as well asalbumin hydrolysis products. Dispersing agents include, for example,lignin sulphite waste liquors and methylcellulose.

Adhesives such as carboxymethylcellulose and natural and syntheticpolymers in the form of powders, granules or latices, such as gumarabic, polyvinyl alcohol and polyvinyl acetate, can be used in theformulations.

It is possible to use colorants such as inorganic pigments, for exampleiron oxide, titanium oxide and Prussian Blue, and organic dyestuffs,such as alizarin dyestuffs, azo dyestuffs or metal phthalocyaninedyestuffs, and trace nutrients, such as salts of iron, manganese, boron,copper, cobalt, molybdenum and zinc.

The formulations in general contain from 0.1 to 95 percent by weight ofactive compound, preferably from 0.5 to 90 percent by weight.

The active compounds according to the invention can be present in theformulations, or in the various use forms, as a mixture with otheractive compounds, such as fungicides, bactericides, insecticides,acaricides, nematicides, herbicides, bird repellents, growth factors,plant nutrients and agents for improving soil structure.

The active compounds can be used as such, as their formulations or asthe use forms prepared therefrom by further dilution, such asready-to-use solutions, emulsions, suspensions, powders, pastes andgranules. They may be used in the customary manner, for example bywatering, spraying, atomising, dusting, scattering, dry dressing, moistdressing, wet dressing, slurry dressing or encrusting.

Especially in the treatment of parts of plants, the active compoundconcentrations in the use forms can be varied within a substantialrange. They are, in general, from 1 to 0.0001% by weight, preferablyfrom 0.5 to 0.001%.

In the treatment of seed, amounts of active compound of in general 0.001to 50 g, preferably 0.01 to 10 g, are generally employed per kilogram ofseed.

For the treatment of soil, active compound concentrations of in general0.00001 to 0.1% by weight, preferably 0.0001 to 0.02%, are employed atthe place of action.

The present invention also provides bactericidal compositions containingas active ingredient a compound of the present invention in admixturewith a solid or liquefied gaseous diluent or carrier or in admixturewith a liquid diluent or carrier containing a surface-active agent.

The present invention also provides a method of combating bacteria(especially phytopathogenic bacteria) which comprises applying to thebacteria, or to a habitat thereof, a compound of the present inventionalone or in the form of a composition containing as active ingredient acompound of the present invention in admixture with a diluent orcarrier.

The present invention further provides crops protected from damage bybacteria by being grown in areas in which immediately prior to and/orduring the time of the growing a compound of the present invention wasapplied alone or in admixture with a diluent or carrier.

It will be seen that the usual methods of providing a harvested crop maybe improved by the present invention.

The preparation of the novel compounds is shown in the followingillustrative examples

EXAMPLE 1 ##STR4##

A solution of 25 g (0.15 mol) of 2-nitro-benzoic acid in 75 ml ofmethanol was added dropwise to a boiling solution of 31 g (0.15 mol) ofdicyclohexyl-carbodiimide and 8 ml of triethylamine in 300 ml ofmethanol. The reaction mixture was heated under reflux for 2 hours andstirred at room temperature overnight. After distilling off the solventin vacuo, the residue was recrystallized from isopropanol. 25 g (45% oftheory) of N-(2-nitrobenzoyl)-N,N'-dicyclohexyl-urea of melting point134° C. were obtained.

The following compounds of the formula (Ia) could be preparedanalogously:

    ______________________________________                                         ##STR5##                     (Ia)                                            Com-                    Melting    Yield                                      pound                   point      (% of                                      No.     R.sup.3         (°C.)                                                                             theory)                                    ______________________________________                                                 ##STR6##       166        33                                         3                                                                                      ##STR7##       204        86                                         4                                                                                      ##STR8##       133        41                                         5                                                                                      ##STR9##       175        56                                         6                                                                                      ##STR10##      190        55                                         7                                                                                      ##STR11##      175        52                                         8                                                                                      ##STR12##      180        47                                         9                                                                                      ##STR13##      143        70                                         10                                                                                     ##STR14##      167        63                                         11                                                                                     ##STR15##      175        50                                         12                                                                                     ##STR16##      175        55                                         13                                                                                     ##STR17##      189        68                                         14                                                                                     ##STR18##      177        43                                         15                                                                                     ##STR19##      154        38                                         16                                                                                     ##STR20##      162        42                                         17                                                                                     ##STR21##      154        59                                         18                                                                                     ##STR22##      165        40                                         19                                                                                     ##STR23##      165        58                                         20                                                                                     ##STR24##      177        47                                         21                                                                                     ##STR25##      145        43                                         22                                                                                     ##STR26##      178        48                                         23                                                                                     ##STR27##      148        62                                         24                                                                                     ##STR28##      158-62     65                                         25                                                                                     ##STR29##      176-80     53                                         26                                                                                     ##STR30##      176-81     57                                         ______________________________________                                    

EXAMPLE 2 ##STR31##

The compound was obtained analogously to Example 1, in a yield of 17% oftheory. The melting point was 238° C.

The bactericidal activity of the compounds of this invention isillustrated by the following examples; the compounds according to thepresent invention are each identified by the number (given in brackets)from the examples hereinabove:

EXAMPLE 3 Xanthomonas oryzae test/bacteriosis/rice

To produce a suitable preparation of active compound, 1 part by weightof active compound was mixed with 25 parts by weight of a solvent(acetone) and 0.75 part by weight of a dispersing agent (alkylarylpolyglycol ether), and the concentrate was diluted with water to thedesired concentration.

Rice plants of the variety Kinmaze which were four weeks old weresprayed with the spray liquid until dripping wet and allowed to dry andthe plants were inoculated with Xanthomonas oryzae by dipping needlesinto an aqueous suspension of the bacteria and pricking the leaves.

After incubation at 100% relative atmospheric humidity for 48 hours, theplants remained in a greenhouse at 24° to 26° C. and 70 to 80% relativeatmospheric humidity for 10 days until they were examined. The degree ofinfection was expressed in percent of the infection of the untreatedcontrol plants: 0% denoted no infection and 100% corresponded to theinfection of the control plants.

In this test, for example, the following compounds showed a superioraction compared with the prior art: compounds (6) and (7).

EXAMPLE 4 Xanthomonas oryzae test/bacteriosis/rice/systemic

To produce a suitable preparation of active compound, 1 part by weightof active compound was mixed with 125 parts by weight of a solvent(acetone) and 3.75 parts by weight of a dispersing agent (alkylarylpolyglycol ether), and the concentrate was diluted with water to thedesired concentration.

Pots 10×10 cm in size which contained rice plants of the variety Kinmazewhich were about 5 weeks old were watered with a definite amount of thispreparation of active compound, the amount of active compound to beapplied being calculated from the surface area of the soil.

3 days after treatment of the soil, the plants were inoculated withXanthomonas oryzae by dipping needles into an aqueous suspension of thebacteria and pricking the leaves. The plants remained in a greenhouse at24° to 26° C. and 70 to 80% relative atmospheric humidity until theywere examined.

The degree of infection was expressed in percent of the infection of theuntreated control plants: 0% denoted no infection and 100% correspondedto the infection of the control plants.

In this test, the following compounds showed a superior action comparedwith the prior art: compounds (1), (4), (7), (8) and (9).

It will be appreciated that the instant specification and examples areset forth by way of illustration and not limitation, and that variousmodifications and changes may be made without departing from the spiritand scope of the present invention.

We claim:
 1. An N-cycloalkyl-N'-substituted-N'-acyl-urea of the formula##STR32## in which R¹ is cyclohexyl,R² is cyclohexyl, phenyl or di-C₁₋₄-alkyl substituted phenyl, and R³ is cyclohexyl, phenyl substituted byC₁₋₄ -alkyl, C₁₋₄ -alkoxy, halogen or C₁₋₂ -haloalkyl, or phenylsubstituted by nitro plus at least one member selected from the groupconsisting of C₁₋₄ -alkyl, C₁₋₄ -alkoxy, halogen or C₁₋₂ -haloalkyl. 2.A compound according to claim 1, in whichR² is cyclohexyl or2,6-dialkyl-phenyl.
 3. A compound according to claim 1, in which saidcompound is N-(4-methylbenzoyl)-N,N'-dicyclohexyl-urea of the formula##STR33##
 4. A compound according to claim 1, in which said compound isN-(3-nitrobenzoyl)-N,N'-dicyclohexyl-urea of the formula ##STR34##
 5. Acompound according to claim 1, in which said compound isN-(4-methyl-3-nitrobenzoyl)-N,N'-dicyclohexyl-urea of the formula##STR35##
 6. A compound according to claim 1, in which said compound isN-(4-chloro-3-nitrobenzoyl)-N,N'-dicyclohexyl-urea of the formula##STR36##
 7. A compound according to claim 1, in which said compound isN-(4-fluorobenzoyl)-N,N'-dicyclohexyl-urea of the formula ##STR37##
 8. Acompound according to claim 1, in which said compound isN-cyclohexylcarbonyl-N,N'-dicyclohexyl-urea of the formula ##STR38## 9.A bactericidal composition containing an active ingredient abactericidally effective amount of a compound of the formula ##STR39##in which R¹ is cyclohexyl,R² is cyclohexyl, phenyl or di-C₁₋₄ -alkylsubstituted phenyl, and R³ is cyclohexyl or phenyl substituted by C₁₋₄-alkyl, C₁₋₄ -alkoxy, halogen or C₁₋₂ -haloalkyl or phenyl substitutedby nitro plus at least one member selected from the group consisting ofC₁₋₄ -alkyl, C₁₋₄ -alkoxy, halogen or C₁₋₂ -haloalkyl, in admixture witha diluent.
 10. A method of combating bacteria which comprises applyingto the bacteria, or to a habitat thereof, a bactericidally effectiveamount of a compound of the formula ##STR40## in which R¹ iscyclohexyl,R² is cyclohexyl, phenyl or di-C₁₋₄ -alkyl substitutedphenyl, and R³ is cyclohexyl or phenyl substituted by C₁₋₄ -alkyl, C₁₋₄-alkoxy, halogen or C₁₋₂ -haloalkyl or phenyl substituted by nitro plusat least one member selected from the group consisting of C₁₋₄ -alkyl,C₁₋₄ -alkoxy, halogen or C₁₋₂ -haloalkyl.
 11. The method according toclaim 10, in which said compoundisN-(4-methylbenzoyl)-N,N'-dicyclohexyl-urea,N-(4-methyl-3-nitrobenzoyl)-N,N'-dicyclohexyl-urea,N-(4-chloro-3-nitrobenzoyl)-N,N'-dicyclohexyl-urea,N-(4-fluorobenzoyl)-N,N'-dicyclohexyl-urea, orN-cyclohexylcarbonyl-N,N'-dicyclohexyl-urea.